1. Field of the Invention
The present invention relates generally to medical methods and devices. More particularly, the present invention relates to methods and systems for treating ischemic cardiac and other tissue damaged by myocardial infarction and other causes by intravascularly injecting therapeutic cells at or near the damaged tissue.
Cardiac tissue can be damaged by a variety of causes, including myocardial infarction, cardiac tissue infections, diseases such as rheumatic fever, trauma, and the like. Extensive damage to myocardial or valve tissues can cause heart failure and death. Present treatments include heart transplantation, valve repair surgery, and drug therapies. None of these treatments, however, is effective for all patients, and heart failure remains a leading cause of death world wide.
Neurologic tissue can also become ischemic due to a number of causes, including blocked arteries, stroke, trauma, and the like.
Chronic limb ischemia is a condition that arises from the inability of diseased arteries to conduct sufficient blood flow to the lower leg, ankle and toes. It can cause persistent, recurring rest pain, ulceration and gangrene. If blood flow cannot be restored by surgical or interventional procedures, patients will eventually require amputation of the affected limb. Recently, a study reported positive results of autologous bone marrow cell transplantation into patients with limb ischemia due to peripheral artery disease.
Such cell therapy apparently provided re-vascularization by promoting development of collateral arteries flowing to the ischemic muscle. Cells were injected intramuscularly requiring the harvest of 500 ml of bone marrow. Such marrow harvest is very traumatic. If cells could be delivered more precisely to the affected muscles and placed in a non-ischemic depot where there viability was maintained, it should be possible to achieve patient benefit with fewer cells. This would reduce patient discomfort associated with the bone marrow procedure and improve dose response.
Much research is focused on developing therapies for inducing or enhancing the repair of damaged cardiac tissues in patients suffering from or at risk of heart failure. Some, such as transmyocardial revascularization, rely on inducing controlled injury to damaged heart tissue in the hope of causing revascularization and tissue regeneration. Other therapies intended to regenerate tissue include systemic and local administration of growth factors, angiogenic factors, and the like, to promote tissue repair.
Of particular interest to the present invention, the introduction of therapeutic cells into damaged cardiac tissues has been proposed. For example, of the injection of pluripotent stem cells, such as embryonic stem cells or mesenchymal adult progenitor cells (MAPC's), has been shown to have therapeutic benefit when introduced into damaged cardiac tissues. Other cells and cell lines which are the subject of current research for cardiac tissue regeneration include cardiomyocytes, fibroblasts, endothelial cells, and skeletal myoblasts.
Despite this promise, the injection of therapeutic stem and other cells presents a number of challenges. Direct injection of the cells to the myocardium through an epicardial surface is difficult, requiring either an open chest or a transthoracic procedure. Open chest procedures are very traumatic, and transthoracic procedures are complicated and limit the ability to precisely locate the site into which the cells are to be injected.
Intracardiac protocols where the therapeutic cells are injected through the endocardial surface have also been proposed. Such inside-the-heart procedures are also complex and require sophisticated intracardial catheters with complicated positioning systems. Even with such advanced systems, the precise delivery of the therapeutic cells to a particular target location can be difficult.
A third alternative which has recently been proposed is to use an arterial infusion catheter to deliver cells within a blood vessel near the site of the damaged tissue. This catheter-based technique relies on blocking blood flow with a balloon and infusing cells distally into the artery. The need for the cells to migrate through the endothelium, however, may be problematic and ultimately limit the success of this approach. Recent studies have also shown that intraluminal delivery of cells results in micro-infarctions due to the extended balloon occlusion of the artery or the embolism of cellular material blocking capillary flow.
For these reasons, it would be desirable to provide improved methods and systems for delivering therapeutic cells to damaged coronary and other tissues. Such methods and systems will preferably be catheter-based and permit introduction of the cells into cardiac and other tissue via the coronary and peripheral vasculature, including both arteries and veins. The methods and systems should further provide for delivering the therapeutic cells to precisely controlled locations within or adjacent to the damaged tissues, and should also provide for direct delivery into the tissue without dilution in the systemic circulation. Preferably, the methods and systems will allow for injection of the therapeutic cells into the space between a blocked artery and an adjacent collateral vessel to promote enlargement of the collateral vessel. Additionally, the cells which are injected and those which proliferate in situ should be able to migrate and distribute from the site of injection into adjacent regions of damaged tissue in order to provide effective therapy. At least some of these objectives will be met by the inventions described hereinafter.
2. Description of the Background Art
The endocardial and epicardial injection of stem and other cells are described in U.S. Pat. Nos. 6,387,369; 6,099,832; 5,602,301; and 5,591,625, and U.S. Patent Publication No. US 2002/0182186. Isolation, purification and culturing of human mesenchymal stem cells are described in U.S. Pat. No. 5,486,359. The full disclosures of each of these patents and patent publication are incorporated herein by reference.
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